Helicobacter pylori infection causes gastritis, peptic ulcer disease, gastric atrophy and gastric cancer. The World Health Organization has classified H. pylori as a Class I carcinogen. In animal models, the progression of H. pylori disease from superficial gastritis to gastric cancer is related to the severity of the host inflammatory response. The identification of H. pylori components and host factors that contribute to the inflammatory response may lead to important insights into the mechanism of peptic ulcer disease and/or gastric malignancy. Heat shock proteins are potent activators of inflammatory cytokine production. Heat shock proteins produced by bacteria and endogenous heat shock proteins produced by damaged tissue cell accumulate in foci of infection and inflammation. Our recent data indicate that Toll-like receptors and CD14 are important in the innate immune response to bacterial heat shock proteins. In this proposal we will investigate the role of Toll-like receptors in the recognition of bacterial heat shock proteins and in the control of bacterial infection and inflammation. Specifically, we will use in vitro and in vivo approaches to investigate the role of heat shock proteins in H. pylori infection and pathogenesis and development of tumors.